Program Official

Principal Investigator

Lawrence C
Awardee Organization

University Of Texas Med Br Galveston
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Cytosine Deamination Adducts and Cancer Etiology

DNA damage drives human genetic disease including cancer. Exogenous chemicals and endogenous reactive molecules can damage DNA bases forming “adducts”. Unrepaired DNA adducts can block DNA synthesis or miscode during polymerase-mediated replication. The landscape of mutations observed in human cancers is dominated by C:G to T:A transition mutations. A major cause of these mutations is the hydrolytic deamination of cytosine and cytosine analogs in DNA to their corresponding uracil analogs, generating a class of cytosine deamination adducts, xU. Endogenous DNA adducts such as xU have proven more difficult to study due to the similarity of these adducts to normal DNA constituents as well as their formation in normal, unperturbed cells and tissues. In this application, we describe innovative new approaches that will allow definitive identification of xU adducts in DNA using mass spectrometry methods. Further, we will measure the formation and repair of such adducts at known cancer-driving mutational hotspots and genome-wide in both normal human cells and cells with known repair defects. We will also examine xU in discard human tissues representing normal, inflamed and diseased specimens. The studies proposed here will provide an unprecedented examination of this important but understudied class of DNA adducts at the level of DNA sequence. The results of the proposed studies could potentially result in clinically useful approaches to examine the damage history of a given tissue, and provide an estimate as to how far the damage had progressed toward the development of tumors. The anticipated results will shed new light on cancer etiology and potentially direct approaches to reduce cancer incidence and provide earlier detection.


  • Sowers ML, Sowers LC. Glioblastoma and Methionine Addiction. International journal of molecular sciences. 2022 Jun 28;23. (13). PMID: 35806160
  • Hsu CW, Sowers ML, Baljinnyam T, Herring JL, Hackfeld LC, Tang H, Zhang K, Sowers LC. Measurement of deaminated cytosine adducts in DNA using a novel hybrid thymine DNA glycosylase. The Journal of biological chemistry. 2022 Mar;298(3):101638. Epub 2022 Jan 25. PMID: 35085553
  • Baljinnyam T, Conrad JW, Sowers ML, Chang-Gu B, Herring JL, Hackfeld LC, Zhang K, Sowers LC. Characterization of a Novel Thermostable DNA Lyase Used To Prepare DNA for Next-Generation Sequencing. Chemical research in toxicology. 2023 Feb 20;36(2):162-176. Epub 2023 Jan 16. PMID: 36647573
  • Hsu CW, Conrad JW, Sowers ML, Baljinnyam T, Herring JL, Hackfeld LC, Hatch SS, Sowers LC. A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates. Nucleic acids research. 2022 Jul 22;50(13):7406-7419. PMID: 35776119
  • Baljinnyam T, Sowers ML, Hsu CW, Conrad JW, Herring JL, Hackfeld LC, Sowers LC. Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming. PloS one. 2022 Aug 29;17(8):e0273509. doi: 10.1371/journal.pone.0273509. eCollection 2022. PMID: 36037209
  • Conrad JW, Sowers ML, Yap DY, Cherryhomes E, Pettitt BM, Khanipov K, Sowers LC. Transition Mutations in the hTERT Promoter Are Unrelated to Potential i-motif Formation in the C-Rich Strand. Biomolecules. 2023 Aug 25;13. (9). PMID: 37759708
  • Sowers ML, Conrad JW, Chang-Gu B, Cherryhomes E, Hackfeld LC, Sowers LC. DNA Base Excision Repair Intermediates Influence Duplex-Quadruplex Equilibrium. Molecules (Basel, Switzerland). 2023 Jan 18;28. (3). PMID: 36770637